Cinacalcet hydrochloride is chemically known as N-[1-(R)-(−)-(1-naphthyl)ethyl]-3-[3(trifluoromethyl)phenyl]-1-aminopropane hydrochloride and has the following structural formula:

Cinacalcet HCl contains a chiral center and the active substance is the R-enantiomer. It is a white to off-white, non-hygroscopic crystalline powder.
Cinacalcet is a calcimimetic which is used to treat secondary hyperparathyroidism as a consequence of chronic renal failure. In addition, the substance is also used for the treatment of hypercalcaemia in patients with parathyroid carcinoma. The synthesis and clinical utility of Cinacalcet is described in U.S. Pat. Nos. 6,011,068, 6,031,003, 6,211,244 and 6,313,146.
In general, it is desirable to incorporate a disintegrant in a solid oral dosage form of a poorly soluble drug like Cinacalcet. The disintegrating agent plays an important role in the formulation of solid oral dosage forms of poorly soluble compounds by promoting breakup of the solid oral dosage forms into smaller fragments in an aqueous environment thereby increasing the available surface area and in turn promoting a rapid release of the drug substance. The following published patent/patent applications on Cinacalcet solid oral dosage forms have highlighted the use of disintegrating agent in the formulation to attain optimum dissolution profile:
Patent publication U.S. Pat. No. 7,829,595 is listed in the FDA's Orange Book for Cinacalcet film coated tablets. The publication recites that Cinacalcet has a very low solubility in water, i.e, between 0.1 mg/ml and 1.6 mg/ml, depending on the pH value. U.S. Pat. No. 7,829,595 further teaches the use of Cinacalcet HCl compositions comprising: (a) from 10% to 40% by weight of Cinacalcet HCl; (b) from 45% to 85% by weight of at least one diluent; (c) from 1% to 5% by weight of at least one binder; (d) from 1% to 10% by weight of at least one disintegrant; and (e) from 0.05% to 5% by weight of at least one additive chosen from glidants, lubricants, and anti-adherents; wherein the percentage by weight is relative to the total weight of the composition.
US 2010/0168247 refers to a method for preparing a solid composite of Cinacalcet, comprising at least one carrier. Further, use of disintegrant in the amount of 10 to 40% is also disclosed.
WO 2012/071535 discloses hard shell capsules containing a granular powder formulation of Cinacalcet which comprises 1-8% of disintegrant.
Also, other patent publications on Cinacalcet like US 2012/0009258 and US 2012/0270949 disclose use of disintegrant in Cinacalcet formulation.
Disintegrating agents are hygroscopic in nature which may pose formulation challenge with moisture sensitive drugs. Typically, disintegrants like Crospovidone, Sodium Starch Glycolate may contain more than or equal to 5% w/w of water content. Further, use of more than 10% w/w of disintegrant in a formulation may lead to softening of tablets during storage. Also, disintegrants are usually not used in amounts of less than 1%, because of failure to achieve disintegration of the dosage form which may impact release profile.
The objective of the present invention was therefore to overcome the above-mentioned disadvantages.
As Cinacalcet hydrochloride is sparingly soluble in water, its formulation without disintegrant or substantially free of disintegrant is challenging due to possible failure of disintegration of the solid dosage form which may adversely affect dissolution and bioequivalence. Overall, a person skilled in the formulation art may not pursue a dosage form with above challenges.
The present inventors have surprisingly developed a disintegrant free solid oral pharmaceutical composition of Cinacalcet without compromising on dissolution properties of the prepared dosage form. The present invention further provides a simple, economical and industrially feasible process for preparing pharmaceutical composition of Cinacalcet.